scholarly journals Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochemical Implications

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Krzysztof Michalak ◽  
Aleksandra Sobolewska-Włodarczyk ◽  
Marcin Włodarczyk ◽  
Justyna Sobolewska ◽  
Piotr Woźniak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Enzyme Activity ◽  
Antibiotic Therapy ◽  
Effective Treatment ◽  
Social Problem ◽  
Fenton Reaction ◽  
Current Paper ◽  
Bivalent Cations

Long-term fluoroquinolone-associated disability (FQAD) after fluoroquinolone (FQ) antibiotic therapy appears in recent years as a significant medical and social problem, because patients suffer for many years after prescribed antimicrobial FQ treatment from tiredness, concentration problems, neuropathies, tendinopathies, and other symptoms. The knowledge about the molecular activity of FQs in the cells remains unclear in many details. The effective treatment of this chronic state remains difficult and not effective. The current paper reviews the pathobiochemical properties of FQs, hints the directions for further research, and reviews the research concerning the proposed treatment of patients. Based on the analysis of literature, the main directions of possible effective treatment of FQAD are proposed: (a) reduction of the oxidative stress, (b) restoring reduced mitochondrion potential ΔΨm, (c) supplementation of uni- and bivalent cations that are chelated by FQs and probably ineffectively transported to the cell (caution must be paid to Fe and Cu because they may generate Fenton reaction), (d) stimulating the mitochondrial proliferation, (e) removing FQs permanently accumulated in the cells (if this phenomenon takes place), and (f) regulating the disturbed gene expression and enzyme activity.

Antioxidant Pathways and Chemical Mechanism of Curcumin

2011 ◽  
Vol 236-238 ◽  
pp. 2311-2314 ◽  
Author(s):  
Yuan Liang Guo ◽  
Xiang Zhou Li ◽  
Chun Tao Kuang
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Antioxidant Activity ◽  
Enzyme Activity ◽  
Free Radicals ◽  
Curcuma Longa ◽  
Chemical Mechanism ◽  
Stress Regulation ◽  
Antioxidant Mechanism ◽  
Related Enzyme

Curcumin, a hydrophobic polyphenol derived from rhizome (turmeric) of the herbCurcuma longa, have been shown to exhibit antioxidant, anticarcinogenic anti-inflammatory, antimicrobial and nephroprotective activities,et al. Among these, its potent antioxidant activity is worthwhile of special attention, because oxidative stress is involved in the pathogenesis of cancer, neurodegenerative diseases,et al. This review focuses on the ways that curcumin exerts its antioxidant activity, including direct chemical reaction with free radicals, chelation with metals ions which results in oxidative stress, regulation of antioxidant-related enzyme activity and gene expression. Meanwhile the disputed chemical antioxidant mechanism is also discussed.

The role of vanin-1 and oxidative stress–related pathways in distinguishing acute and chronic pediatric ITP

Blood ◽  
2011 ◽  
Vol 117 (17) ◽  
pp. 4569-4579 ◽  
Author(s):  
Bing Zhang ◽  
Clara Lo ◽  
Lei Shen ◽  
Ruchira Sood ◽  
Carol Jones ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Gene Expression Analysis ◽  
Mononuclear Cells ◽  
Stress Sensor ◽  
Chronic Itp ◽  
Acute Itp ◽  
And Oxidative Stress

Abstract Pediatric immune thrombocytopenia (ITP) is usually self-limited. However, approximately 20% of children develop chronic ITP, which can be associated with significant morbidity because of long-term immunosuppression and splenectomy in refractory cases. To explore the molecular mechanism of chronic ITP compared with acute ITP, we studied 63 pediatric patients with ITP. Gene expression analysis of whole blood revealed distinct signatures for acute and chronic ITP. Oxidative stress–related pathways were among the most significant chronic ITP-associated pathways. Overexpression of VNN1, an oxidative stress sensor in epithelial cells, was most strongly associated with progression to chronic ITP. Studies of normal persons demonstrated VNN1 expression in a variety of blood cells. Exposure of blood mononuclear cells to oxidative stress inducers elicited dramatic up-regulation of VNN1 and down-regulation of PPARγ, indicating a role for VNN1 as a peripheral blood oxidative stress sensor. Assessment of redox state by tandem mass spectrometry demonstrated statistically significant lower glutathione ratios in patients with ITP versus healthy controls; lower glutathione ratios were also seen in untreated patients with ITP compared with recently treated patients. Our work demonstrates distinct patterns of gene expression in acute and chronic ITP and implicates oxidative stress pathways in the pathogenesis of chronic pediatric ITP.

scholarly journals Correlation between intermediary metabolism, Hsp gene expression, and oxidative stress-related proteins in long-term thermal-stressed Mytilus galloprovincialis

2020 ◽  
Vol 319 (3) ◽  
pp. R264-R281
Author(s):  
Konstantinos Feidantsis ◽  
Ioannis A. Giantsis ◽  
Andreas Vratsistas ◽  
Stavroula Makri ◽  
Athanasia-Zoi Pappa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Lipid Peroxidation ◽  
Antioxidant Enzymes ◽  
Thermal Stress ◽  
Mytilus Galloprovincialis ◽  
Intermediary Metabolism ◽  
Related Proteins ◽  
And Oxidative Stress

Long-term exposure of Mytilus galloprovincialis to temperatures beyond 26°C triggers mussel mortality. The present study aimed to integratively illustrate the correlation between intermediary metabolism, hsp gene expression, and oxidative stress-related proteins in long-term thermally stressed Mytilus galloprovincialis and whether they are affected by thermal stress magnitude and duration. We accordingly evaluated the gene expression profiles, in the posterior adductor muscle (PAM) and the mantle, concerning heat shock protein 70 and 90 ( hsp70 and hsp90), and the antioxidant defense indicators Mn-SOD, Cu/Zn-SOD, catalase, glutathione S-transferase, and the metallothioneins mt-10 and mt-20. Moreover, we determined antioxidant enzyme activities, oxidative stress through lipid peroxidation, and activities of intermediary metabolism enzymes. The pattern of changes in relative mRNA expression levels indicate that mussels are able to sense thermal stress even when exposed to 22°C and before mussel mortality is initiated. Data indicate a close correlation between the magnitude and duration of thermal stress with lipid peroxidation levels and changes in the activity of antioxidant enzymes and the enzymes of intermediary metabolism. The gene expression and increase in the activities of antioxidant enzymes support a scenario, according to which exposure to 24°C might trigger reactive oxygen species (ROS) production, which is closely correlated with anaerobic metabolism under hypometabolic conditions. Increase and maintenance of oxidative stress in conjunction with energy balance disturbance seem to trigger mussel mortality after long-term exposure at temperatures beyond 26°C. Eventually, in the context of preparation for oxidative stress, certain hypotheses and models are suggested, integrating the several steps of cellular stress response.

scholarly journals Detection of Autophagy-Related Gene Expression by Conjunctival Impression Cytology in Age-Related Macular Degeneration

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 296
Author(s):  
Chih-Wen Shu ◽  
Youn-Shen Bee ◽  
Jiunn-Liang Chen ◽  
Chui-Lien Tsen ◽  
Wei-Lun Tsai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cell Viability ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Autophagic Flux ◽  
Related Gene ◽  
Impression Cytology ◽  
Conjunctival Impression Cytology

Purpose: To investigate the association of autophagy-related gene expression with age-related macular degeneration (AMD). Methods: Patients with AMD were recruited for analysis by conjunctival impression cytology. mRNA was assessed by real-time polymerase chain reaction (RT-PCR) to evaluate whether the expression of 26 autophagy-related genes (ATGs) was correlated with AMD. Further studies on cell viability and autophagic flux in response to oxidative stress by H2O2 were performed in human retinal pigment epithelial (RPE) cell lines based on the results of impression cytology. Results: Both the neovascular AMD (nAMD) and polypoidal choroidal vasculopathy (PCV) groups had significantly higher mRNA levels of gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1) and microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) than the control group, but there was no significant difference between these two groups. Age difference existed only in the AMD group. GABARAPL1 and MAP1LC3B mRNA expression increased significantly after acute oxidative stress in adult retinal pigment epithelial (ARPE-19) cells. Cell viability significantly increased and decreased in the cells harboring GABARAPL1 expression vector and silenced with siRNA against GABARAPL1, respectively, during short-term oxidative stress, whereas viability increased in the GABARAPL1-silenced cells after long-term oxidative stress. Silencing GABARAPL1 itself caused a reduction in autophagic flux under both short and long-term oxidative stress. Conclusion: Our study showed the possibility of assessing autophagy-related gene expression by conjunctival impression cytology. GABARAPL1 was significantly higher in AMD. Although an in vitro study showed an initial protective effect of autophagy, a cell viability study revealed the possibility of a harmful effect after long-term oxidative injury. The underlying mechanism or critical factors require further investigation.

Oxidative stress and cell death in the cerebral cortex as a long-term consequence of neonatal hypoglycemia

2016 ◽  
Vol 94 (9) ◽  
pp. 1015-1022 ◽  
Author(s):  
T.R. Anju ◽  
P.R. Akhilraj ◽  
C.S. Paulose
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cell Death ◽  
Cerebral Cortex ◽  
Real Time ◽  
Real Time Pcr ◽  
Caspase 3 ◽  
Neonatal Hypoglycemia ◽  
Old Rats

Neonatal hypoglycemia limits glucose supply to cells leading to long-term consequences in brain function. The present study evaluated antioxidant and cell death factors’ alterations in cerebral cortex of 1-month-old rats exposed to neonatal hypoglycemia. Gene expression studies by real-time PCR were carried out using gene-specific TaqMan probes. Fluorescent dyes were used for immunohistochemistry and nuclear staining and imaged by confocal microscope. Total antioxidant level and expression of antioxidant enzymes — superoxide dismutase (SOD) and gluthathione peroxide (GPx) — mRNA was significantly reduced along with high peroxide level in the cerebral cortex of 1-month-old rats exposed to neonatal hypoglycemia. Real-time PCR analysis showed an upregulation of Bax, caspase 3, and caspase 8 gene expression. Confocal imaging with TOPRO-3 staining and immunohistochemistry with caspase 3 antibody indicated cell death activation. The reduced free radical scavenging capability coupled with the expression of key factors involved in cell death pathway points to the possibility of oxidative stress in the cortex of 1-month-old rats exposed to neonatal hypoglycemia. The observed results indicate the effects of neonatal hypoglycemia in determining the antioxidant capability of cerebral cortex in a later stage of life.

scholarly journals Identification of Differentially Expressed Genes and Processes in Myocardial Tissue of Liver-Specific Gck Knockout Mice

2020 ◽  
Author(s):  
Hui Li ◽  
Wei Xu ◽  
Yiqing Mao ◽  
Xi Wang ◽  
Ruoxuan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Enzyme Activity ◽  
Knockout Mice ◽  
Myocardial Injury ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Expression Profiles ◽  
Left Ventricular ◽  
Significant Difference

Abstract Background: Diabetic cardiomyopathy is a ventricular disease caused by diabetes mellitus. Abnormalities in the function of the glucokinase (GCK) play an important role in the development of diabetes. The present study is aimed at exploring changes in gene expression and related molecular mechanisms of diabetic myocardial injury in Gck knockout mice. Methods: Liver-specific glucokinase gene knockout mice( Gck w/- ) and wide type ( Gck w/w )mice generated using the Cre-loxP gene targeting strategy of 30- and 60-weeks of age were used in these studies. Determination of liver glucokinase enzyme activity, liver glycogen content and serum biochemistry parameters reflect the metabolic disorder in these mice. Echocardiography and surface electrocardiographs were used to evaluate cardiac function. Superoxide dismutase activity and malondialdehyde levels reflect oxidative stress in the myocardium. RNAseq, GO enrichment analysis and qPCR wereused to detect differences in the myocardial gene expression profiles of Gck w/- and Gck w/w mice. Results: Hyperglycemia and insulin resistance induced by decreased liver glucokinase expression and enzyme activity throughout the life of heterozygous Gck knockout mice do not yield body weight significant difference. However, prolonged PR interval and QRS duration, decreased left ventricular diameter and increased thickness of the posterior wall of the left ventricle were accompanied by increase of PAS and Masson positive substances in the myocardium of 60-week-old Gck knockout mice. RNAseq analysis showed that genes related tothe myosin heavy and light chains, insulin signaling pathway and oxidative phosphorylation were significantly differentially expressedbetween60-week-old Gck w/- and Gck w/w mice. Phosphorylation of AMPKβ1 and ACC in 60-week-old Gck knockout mice was decreased. Conclusions: Liver-specific Gck knock-out can induce myocardial fibrosis at an early stage and diabetic myocardial injury at alate stage. Through this process, the proportion of myosin heavy chain and light chain falls out of balance, the insulin signal pathway becomes down regulated and mitochondrial oxidative stress is up regulated, leading to myocardial disease.

scholarly journals Genes regulating biochemical pathways of oxygen metabolism in porcine oviductal epithelial cells during long-term IVC

2019 ◽  
Vol 7 (2) ◽  
pp. 39-47
Author(s):  
Ievgeniia Kocherova ◽  
Maciej Brązert ◽  
Patrycja Sujka-Kordowska ◽  
Aneta Konwerska ◽  
Magdalena Kulus ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Epithelial Cells ◽  
Reproductive System ◽  
Cellular Response ◽  
Polycystic Ovary ◽  
Primary Cultures ◽  
Oxygen Metabolism ◽  
Main Trend

AbstractOxygen metabolism has an important role in the normal functioning of reproductive system, as well as the pathogenesis of female infertility. Oxidative stress seems to be responsible for the initiation or development of reproductive organ diseases, including polycystic ovary syndrome, endometriosis, preeclampsia, etc. Given the important role of maintaining balance between the production of ROS and antioxidant defence in the proper functioning of reproductive system, in the present study we aimed to analyse the expression of genes related to oxygen metabolism in porcine oviductal epithelial cells during long-term in vitro culture. The oviducts were collected from 45 crossbred gilts at the age of approximately nine months that displayed at least two regular oestrous cycles. The oviductal endothelial cells were isolated by enzymatic digestion to establish long-term primary cultures. Gene expression changes between 7, 15 and 30 daysof culturewere analysed with the use ofwhole transcriptome profiling by Affymetrix microarrays. The most of the “cellular response to oxidative stress” genes were upregulated. However, we did not observe any main trend in changes within the “cellular response to oxygen-containing compound” ontology group, where the gene expression levels were changed in various manner.Running title: Oxygen metabolism in porcine oviductal epithelial cells

Oxygen Radicals as Messengers in Oxygen-Dependent Gene Expression

Physiology ◽  
2000 ◽  
Vol 15 (4) ◽  
pp. 202-208 ◽  
Author(s):  
Thomas Kietzmann ◽  
Joachim Fandrey ◽  
Helmut Acker
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Fenton Reaction ◽  
Oxygen Radicals ◽  
Gene Activity ◽  
Cellular Functions

Changes in ambient Po2need to be sensed to allow long-term adaptation of cellular functions via the regulation of gene activity. The generation of OH• from H2O2in an iron-dependent perinuclear Fenton reaction for triggering gene expression could be the key event in the O2signaling pathway.

scholarly journals Immediate Transcriptional Response to a Temperature Pulse under a Fluctuating Thermal Regime

2019 ◽  
Vol 59 (2) ◽  
pp. 320-337
Author(s):  
Dacotah Melicher ◽  
Alex S Torson ◽  
Tanner J Anderson ◽  
George D Yocum ◽  
Joseph P Rinehart ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Thermal Regime ◽  
Low Temperatures ◽  
Transcriptional Response ◽  
Temperature Cycle ◽  
Cold Temperatures ◽  
Temperature Pulse ◽  
Single Temperature

Abstract The response of ectotherms to temperature stress is complex, non-linear, and is influenced by life stage and previous thermal exposure. Mortality is higher under constant low temperatures than under a fluctuating thermal regime (FTR) that maintains the same low temperature but adds a brief, daily pulse of increased temperature. Long term exposure to FTR has been shown to increase transcription of genes involved in oxidative stress, immune function, and metabolic pathways, which may aid in recovery from chill injury and oxidative damage. Previous research suggests the transcriptional response that protects against sub-lethal damage occurs rapidly under exposure to fluctuating temperatures. However, existing studies have only examined gene expression after a week or over many months. Here we characterize gene expression during a single temperature cycle under FTR. Development of pupating alfalfa leafcutting bees (Megachile rotundata) was interrupted at the red-eye stage and were transferred to 6°C with a 1-h pulse to 20°C and returned to 6°C. RNA was collected before, during, and after the temperature pulse and compared to pupae maintained at a static 6°C. The warm pulse is sufficient to cause expression of transcripts that repair cell membrane damage, modify membrane composition, produce antifreeze proteins, restore ion homeostasis, and respond to oxidative stress. This pattern of expression indicates that even brief exposure to warm temperatures has significant protective effects on insects exposed to stressful cold temperatures that persist beyond the warm pulse. Megachile rotundata’s sensitivity to temperature fluctuations indicates that short exposures to temperature changes affect development and physiology. Genes associated with developmental patterning are expressed after the warm pulse, suggesting that 1 h at 20°C was enough to resume development in the pupae. The greatest difference in gene expression occurred between pupae collected after the warm pulse and at constant low temperatures. Although both were collected at the same time and temperature, the transcriptional response to one FTR cycle included multiple transcripts previously identified under long-term FTR exposure associated with recovery from chill injury, indicating that the effects of FTR occur rapidly and are persistent.

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